A rare case of Cryptococcus luteolus-related tenosynovitis.

A 68-year-old male with type II diabetes mellitus presented with a nodule over the metacarpophalangeal joint of his right second finger after being spurred on the hand by a domestic turkey 2 weeks prior to onset of clinical symptoms. He was diagnosed with cryptococcal tenosynovitis caused by Cryptococcus luteolus identified by DNA sequencing. Complete clinical resolution was achieved with synovectomy and debridement followed by 1 year of fluconazole 800 mg daily.

Lichenoid histopathologic changes in patients with clinical diagnoses of exfoliative dermatitis.

Among 30 patients who received a clinical diagnosis of exfoliative dermatitis and were biopsied between 1982 and 1990, nine showed microscopic features of lichenoid dermatitis. Clinical information was available in eight of these cases. Possible etiologic factors included lymphoma, herpes simplex infection, connective tissue disease, and (in five cases) reactions to drugs. In each instance, microscopic features included a superficial perivascular lymphocytic infiltrate involving the dermal-epidermal interface, vacuolar alteration of the basilar layer, and individually necrotic keratinocytes at all levels of the epidermis. Such microscopic changes are not usually described in connection with exfoliative dermatitis, with the possible exception of those cases related to lichen planus or lupus erythematosus. Disseminated lichenoid drug eruption is one possible interpretation of the drug-induced cases. Erythema multiforme is another condition that has similar microscopic features and has been associated with drugs (many of which also cause exfoliative dermatitis), infectious agents, neoplasms, and connective tissue diseases. Lichenoid dermatitis can become generalized and clinically mimic and exfoliative dermatitis. Many, but not all, of these eruptions may be triggered by drugs.

Pressure dermatitis from an implanted pacemaker.

In this eleventh report of dermatitis conforming to the outline of an underlying pacemaker, the authors suggest that most of these reactions are isomorphic responses to expansion of the subcutaneous tissues by the hard device. Allergic contact dermatitis has been documented in a few cases.

Red lunulae revisited: a clinical and histopathologic examination.

Red lunulae are associated with rheumatoid arthritis, systemic lupus erythematosus, alopecia areata, cardiac failure, hepatic cirrhosis, lymphogranuloma venereum, psoriasis, carbon monoxide poisoning, twenty-nail dystrophy, and reticulosarcoma. We examined four patients with red lunulae. Three had chronic obstructive pulmonary disease. Two of these three were alcohol abusers and were without any of the conditions previously associated with red lunulae. Two of the four also had palmar erythema. Histopathologic examination of the red lunula in one of the four cases did not show signs of neovascularization. We report our findings in these patients, which suggest that red lunulae result from increased arteriolar blood flow, a vasodilatory capacitance phenomenon, or changes in the optical properties of the overlying nail so that normal blood vessels become more apparent.

Dinitrochlorobenzene is inherently mutagenic in the presence of trace mutagenic contaminants.

2,4-Dinitrochlorobenzene (DNCB) is used for immunotherapy of alopecia areata and verruca vulgaris. We initially postulated that the presence of mutagenic contaminants in commercially available DNCB might account for part of its mutagenicity. We have now characterized changes in the dose-mutagenic response curve of 99% DNCB modified by adding 1% concentrations of known contaminants: 1-chloro-2-nitrobenzene; 1,3-dinitrobenzene; and 2,4-dichloronitrobenzene. Dose-response curves were generated using Salmonella typhimurium tester strains TA-98 and TA-100 at concentrations of 0, 1, 5, 10, 25, 50, and 100 micrograms per plate in a modified Ames assay. We observed a linear dose-response relationship with a slight, but nonsignificant, shift to the right when contaminants were added. We conclude that DNCB is itself mutagenic, and that contaminants play a minor role in its observed mutagenicity.

Herpes zoster as a sign of AIDS-related complex.

Herpes zoster has recently been reported in young patients with risk factors for AIDS. In high-risk patients under age 55, herpes may be the first manifestation of AIDS or AIDS-related complex. Dissemination of zoster does not appear to be greatly increased in this group, but corticosteroid therapy should be withheld.

Assessment of diphenylcyclopropenone for photochemically induced mutagenicity in the Ames assay.

The photochemical conversion of diphenylcyclopropenone to diphenylacetylene has recently been reported. Diphenylcyclopropenone is used in the treatment of alopecia areata and is nonmutagenic in a limited Ames assay. We examined diphenylcyclopropenone and diphenylacetylene, as well as synthetic precursors of diphenylcyclopropenone--dibenzylketone and alpha,alpha'-dibromodibenzylketone--for mutagenicity against TA100, TA98, TA102, UTH8413, and UTH8414. All compounds were nonmutagenic except alpha,alpha'-dibromodibenzylketone, which was a potent mutagen in TA100 with and without S-9 activation. The effect of photochemical activation of diphenylcyclopropenone in the presence of bacteria demonstrated mutagenicity in UTH8413 (two times background) at 10 micrograms/plate with S-9 microsomal activation. 8-Methoxypsoralen produces a mutagenic response in TA102 at 0.1 microgram/plate with 60 seconds of exposure to 350 nm light. In vitro photochemically activated Ames assay with S-9 microsomal fraction may enhance the trapping of short-lived photochemically produced high-energy mutagenic intermediates. This technique offers exciting opportunities to trap high-energy intermediates that may play an important role in mutagenesis. This method can be applied to a variety of topically applied dermatologic agents, potentially subjected to photochemical changes in normal use.

Squaric acid and esters: analysis for contaminants and stability in solvents.

Two squaric acid diesters, squaric acid diethyl ester (SADEE) and squaric acid dibutyl ester (SADBE), have been suggested as replacements for 2,4-dinitrochlorobenzene in the treatment of alopecia areata and alopecia totalis. We synthesized these squaric acid diesters and examined them for the presence of carcinogenic contaminants, hexachlorobutadiene and tetrachloro-2-cyclobutene-1-one, by gas chromatography-mass spectrometry (GC-MS). The stability of SADBE to hydrolysis by water in acetone, butanol, isopropanol, and absorbent ointment with and without molecular sieves was examined. The stability of SADEE in ethanol and acetone, with and without molecular sieves, was also studied. Hydrolysis products were detected by their formation of a colored complex with ferric chloride. This complex absorbs in the visual range at 480 nm, thus affording a convenient method for determination of the concentration of free squaric acid in a solution. No contaminants were found by positive or negative ion detection in our GC-MS system. At the end of 3 weeks the extent of hydrolysis was greater in alcohols than in acetone when 10 and 100 molar excess of water were added to the solutions. In the presence of molecular sieves, hydrolysis was reduced even at 100 molar excess of added water in alcohol ar acetone. However, under storage conditions without sieves, acetone solutions and alcohol solutions were equally stable over a period of 2 months. Molecular sieves reduce hydrolysis of squarate esters in the presence of a large molar excess of water, regardless of solvent.

Diphenylcyclopropenone: examination for potential contaminants, mechanisms of sensitization, and photochemical stability.

Diphenylcyclopropenone (DPCP) has recently been reported to be a potent contact sensitizer for the treatment of alopecia areata. DPCP is nonmutagenic in the Ames assay. Studies on chemical purity, stability, and mechanisms of action are lacking. DPCP is synthesized by cyclization of alpha, alpha'-dibromodibenzylketone. The latter elicits a reaction in guinea pigs sensitized to DPCP. We examined a commercial sample of DPCP by gas chromatography--mass spectrometry for the presence of contaminants. The stability of dilute solutions of DPCP in ethanol and cyclohexane to fluorescent light, sunlight, and heat was followed by ultraviolet (UV) spectrometry. The isosbestic point and half-life for this reaction were determined. We found no original or intermediate reagents in our sample. DPCP was found to decompose, forming diphenylacetylene on exposure to both sunlight and fluorescent light in less than 2 weeks. Samples shielded from the light at -70 degrees C and at room temperature were stable over a 4-week period. The extent of decomposition was the same in both ethanol and cyclohexane. It is possible that DPCP may act as a prosensitizer with the actual sensitizer liberated by a photoactivated intermediate (stable, metastable, or unstable) or a combination of these.

Actinic keratoses.

Actinic keratoses are premalignant lesions of the epidermis arising on sun-damaged skin. Sun exposure, skin color, tanning ability and heredity are important factors in their development. Actinic keratoses must be distinguished from seborrheic keratoses, squamous cell and basal cell carcinomas and keratoacanthomas. Treatment depends on the location and the extent of disease.

Contaminants of dinitrochlorobenzene.

DNCB (2,4-dinitrochlorobenzene) is used in the treatment of alopecia areata, recalcitrant verrucae, and for evaluating immunocompromised patients. Currently, there is no pharmaceutical grade of DNCB available for clinical use. Recently, no nitrochlorobenzene contamination was found with the use of positive ion detection gas chromatography--mass spectrometry. We examined six commercial sources of DNCB, with the use of negative ion detection gas chromatography--mass spectrometry, for volatile impurities such as nitrochlorobenzene which might remain from the manufacturing process. The use of negative ion detection increases the sensitivity of this technic to benzene rings substituted with electron withdrawing groups like the nitrochlorobenzenes. We found that all sources of DNCB contain various combinations of nitrochlorobenzene, dinitrobenzene, nitrodichlorobenzene, and other isomers of DNCB. Nitrochlorobenzene has been shown to be mutagenic in the Ames test and carcinogenic in animal studies. The presence of nitrochlorobenzene and other contaminants in commercial grades of DNCB raises questions about the continued clinical application of this agent.

Synthesis and biological evaluation of neutral derivatives of 5-fluoro-2'-deoxyuridine 5'-phosphate.

5-Fluoro-5'-(2-oxo-1,3,2-oxazaphosphorinan-2-yl)-2'-deoxyuridine (1a) and 5-fluoro-5'-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2'-deoxyuridine (1b) were prepared by reaction of 5-fluoro-2'-deoxyuridine (7a) and phosphoryl chloride with 3-amino-1-propanol and 1,3-propanediol, respectively. The thymidine analogues, 1c and 1d, were prepared similarly from thymidine. Compound 1b was synthesized in better yield from 13a and trimethylene phosphate with triphenylphosphine/diethyl azodicarboxylate as a condensing agent. Compounds 1a-d were resistant to degradation by 5'-nucleotidase, alkaline phosphatase, venom phosphodiesterase, and crude snake venom. None of these compounds were significantly biotransformed when incubated with mouse hepatic microsomal preparations in the presence of an NADPH-generating system. When administered intraperitoneally (ip) for 5 consecutive days, 1a was nearly as effective as 5-fluorouracil at prolonging the life spans of BDF1 mice implanted intraperitoneally with leukemia P-388. However, much larger dosages of 1a were required for optimal activity. Compound 1b administered similarly was only marginally effective. Neither 1a nor 1b was active against a P-388 mutant resistant to 5-fluorouracil.